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Title: Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia
Authors: Han Y.
Dorajoo R. 
Chang X. 
Wang L.
Khor C.-C.
Sim X. 
Cheng C.-Y. 
Shi Y. 
Tham Y.C. 
Zhao W. 
Chee M.L.
Sabanayagam C.
Chae M.L.
Tan N.
Wong T.Y.
Tai E.-S. 
Liu J. 
Goh D.Y.T. 
Yuan J.-M.
Koh W.-P.
Van Dam R.M.
Low A.F.
Chan M.Y.-Y.
Friedlander Y.
Heng C.-K. 
Keywords: APOA5 protein, human
apolipoprotein A5
biological marker
case control study
coronary artery disease
ethnic group
follow up
genetic predisposition
genome-wide association study
middle aged
missense mutation
prospective study
single nucleotide polymorphism
Southeast Asia
very elderly
Aged, 80 and over
Apolipoprotein A-V
Asia, Southeastern
Case-Control Studies
Coronary Artery Disease
Ethnic Groups
Follow-Up Studies
Genetic Predisposition to Disease
Genome-Wide Association Study
Middle Aged
Mutation, Missense
Polymorphism, Single Nucleotide
Prospective Studies
Issue Date: 2017
Citation: Han Y., Dorajoo R., Chang X., Wang L., Khor C.-C., Sim X., Cheng C.-Y., Shi Y., Tham Y.C., Zhao W., Chee M.L., Sabanayagam C., Chae M.L., Tan N., Wong T.Y., Tai E.-S., Liu J., Goh D.Y.T., Yuan J.-M., Koh W.-P., Van Dam R.M., Low A.F., Chan M.Y.-Y., Friedlander Y., Heng C.-K. (2017). Genome-wide association study identifies a missense variant at APOA5 for coronary artery disease in Multi-Ethnic Cohorts from Southeast Asia. Scientific Reports 7 (1) : 17921. ScholarBank@NUS Repository.
Abstract: Recent genome-wide association studies (GWAS) have identified multiple loci associated with coronary artery disease (CAD) among predominantly Europeans. However, their relevance to multi-ethnic populations from Southeast Asia is largely unknown. We performed a meta-analysis of four GWAS comprising three Chinese studies and one Malay study (Total N = 2,169 CAD cases and 7,376 controls). Top hits (P < 5 × 10-8) were further evaluated in 291 CAD cases and 1,848 controls of Asian Indians. Using all datasets, we validated recently identified loci associated with CAD. The involvement of known canonical pathways in CAD was tested by Ingenuity Pathway Analysis. We identified a missense SNP (rs2075291, G > T, G185C) in APOA5 for CAD that reached robust genome-wide significance (Meta P = 7.09 × 10-10, OR = 1.636). Conditional probability analysis indicated that the association at rs2075291 was independent of previously reported index SNP rs964184 in APOA5. We further replicated 10 loci previously identified among predominantly Europeans (P: 1.33 × 10-7-0.047). Seven pathways (P: 1.10 × 10-5-0.019) were identified. We identified a missense SNP, rs2075291, in APOA5 associated with CAD at a genome-wide significance level and provided new insights into pathways contributing to the susceptibility to CAD in the multi-ethnic populations from Southeast Asia. © 2017 The Author(s).
Source Title: Scientific Reports
ISSN: 20452322
DOI: 10.1038/s41598-017-18214-z
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